Method of preparing organic phosphonates by transesterification



United States Patent No Drawing. Filed Mar. 4, 1963, Ser. No. 262,340 5 Claims. (Cl. 260-982) This invention pertains to a method of preparing esters of phosphonic acids. In particular, the invention is concerned with the preparation of mixed alkyl aryl phosphonates.

As heretofore practiced, the production of mixed phosphonates has entailed a two-fold operation in which each esterifying alcohol is separately introduced into the phosphonic acid molecule. In a typical synthesis, a phosphonic dichloride is first reacted with the requisite alcohol in the presence of a base whereby one of the chlorine atoms is replaced by the alkoxyl function provided by the particular esterifying alcohol. From this reaction there is obtained an intermediate phosphonochloridate which after being isolated is once more subjected to esterification as above described and the remaining chlorine replaced by a second and different alcoholic function.

Although the two-stage esterification of phosphonic dichloride appears to offer a general synthetic route for the production of mixed phosphonate esters, the reaction is subject to a considerable degree of variation. This is especially true with respect to yields of final product. Such a variation in yield stems primarily from the difliculties encountered in isolating the intermediate phosphonochloridate, a factor which has been found to differ markedly in individual cases. In this connection, it is interesting to refer to a rather recent article in the JACS, 80, 3948 (195 8), in which the authors report the preparation of O-isopropyl ethylphosphonochloridothioate by the stepwise reaction of a phosphonic chloride with alcohols. Even after several attempts making use of different reaction conditions, the highest yield reported amounted to only 12.5%.

Manifestly, the organophosphorus art would be extended and benefited if mixed phosphonate esters could be obtained in higher yields and with greater reliability than is realizable by the presently known methods.

It has now been discovered that mixed phosphonates wherein one of the esterifying moieties is aryl and the other alkyl are realizable by a process which does away with the step-wise reaction of alcohol with a phosphonic dichloride thereby eliminating the difficulties attendant the isolation of an intermediate phosphonochloridothioate. In accordance with the present invention, excellent yields of mixed aryl alkyl phosphonates can be achieved by subjecting under anhydrous conditions a diaryl phosphonate to a transesterification reaction in the presence of an alkali metal salt of a weak acid which functions as a catalyst, whereby one of the aryl groups is replaced by an alkyl radical derived from the esterifying alcohol. The reaction which is of general applicability can be schematically depicted by the following chemical equallOll 2 X 0 Ar 0 Ar II R 0 H p R P H O A r alkali metal salt of 0 Ar weak acid as catalyst O R 3,272,892 Patented Sept. 13, 1966 ice wherein R and R represent alkyl radicals of from 1 to 20 carbon atoms, e.g. methyl, ethyl, n-propyl, isopropyl, sec.- butyl, tert.-butyl, n-amyl, tert.-amyl, sec.-emyl, n-hexyl, isohexyl, isooctyl, n-nonyl, n-decyl, n-tridecyl, n-tetradecyl, pentadecyl, hexadecyl, octadecyl, etc., X is a chalcogen such as sulfur or oxygen, and Ar represents an aromatic hydrocarbon residue of the benzene and naphthalene series.

In preparing the mixed aryl alkyl phosphonates in accordance with the transesterifi-cation reaction as contemplated herein, it has been ascertained that a high degree of reproducibility accompanied by superior yields results by heating in the presence of an alkali metal alkoxide catalyst a diaryl phosphonate with an aliphatic alcohol having an alkyl radical identical to the alkyl group of the desired aryl alkyl phosphonate. A convenient and simple procedure consists in refluxing the diaryl phosphonate in the aliphatic alcohol containing a catalytic quantity of sodium alkoxide derived from the particular alcohol utilized in the transesterification. After removing the phenolic by-product of the transesterification, the so-obtained mixed aryl alkyl phosphonate is separated and isolated by means of techniques commonly employed in the organic chemistry art, such as crystallization, sub limation, distillation and the like.

The diarylp'hosphonates, which serve as intermediates for the transesterification process of the invention, are known chemical entities, the preparation and description of which can be found in the technical literature and various chemical brochures and textbooks. Normally such materials are formed by reacting under basic conditions about one mole of a phosphonic dichloride with at least two moles of a phenolic reactant. For a more detailed account of the synthesis of diarylphosphonates, reference is made to the well known treatise, Organophosphorus Compounds, by G. H. Kosolapoff.

Reference is now made to the following examples which are presented for the purpose of illustration only since variations in practicing the invention without departing from the spirit or scope thereof will be apparent to those skilled in the art to which the said invention pertains.

Example 1 O-isopropyl O-2-chloro4-nltrophenyl ethylphosphonothioate 122 g. (0.28 M) of 0,0-bis(2-chloro-4 nitrophenyl) ethylphosphonothioate was mixed with 300 ml. of isopropanol--previously reacted with 2 g. of sodium-and the resulting mixture refluxed for a period of 56 hours, during which interval the initially insoluble starting material underwent gradual dissolution. After distilling off the isopropanol, the residue was taken up in 250 ml. of benzene, the organic solution washed with 600 ml. of 2% sodium hydroxide, then with water and the organic layer dried over anhydrous magnesium sulfate and the solvent removed by distillation. There was obtained 72 g. of a light brown residue having a refractive index of 1.5582. On cooling and inoculation, the product solidi- The above depicted compound was obtained by refluxficd, and after crystallization from hexane melted at 48 ing for 100 hours a mixture of 43.7 g. of 0,0-bis(2- C. The analysis of the purified product was in conchloro-4-nitrophenyl)ethylphosphonothioate and 100 ml. sonance with the above depicted structure. of sec.-butanol previously reacted with 1.2 g. of metallic The 2-chloro-4-nitrophenol formed as a by-product dur- 5 sodium. There was obtained in 76% yield a brown oil ing the transesterification can be recovered from the alkaexhibiting a refractive index of 1.5487 at 25 C. line aqueous phase by acidification for preparing additional diarylphosphonate for use as starting material in Example 7 further preparations.

Example 2 1O 4 v S l CH3 0-2-chloro4-nltropheny1 O-n-butyl ethylphosphonothioate The precedure for this preparation was patterned after Example 1 but using 50 g. (0.118 M) of 0,0-bis(2- The above depicted compound was prepared by refluxchloro-4-nitrophenyl) ethylphosphonothioate and 100* ml. ing for 32 hours diphenyl phenylphosphonate and isoproof n-butanol previously reacted with 0.5 g. of sodium. panol in accordance with the procedures of the previous Odsopropyl O-phenyl phenylphosphonate The mixture was refluxed at 115120 C. for six hours. examples. The light brown, oily product was obtained in a yield of In general, it has been ascertained that any weak acid 85%; the N is 1.5422. salt which is capable of forming the phenoxide ion from Example 3 r the liberated phenol is satisfactory as a catalyst. It is 20 the phenoxide ion itself which constitutes the direct and CH3 S active catalyst in the transesterification system. Particularly suitable for the aforesaid purpose are the alkali NO1 metal salts of weak acids, e.g. sodium alkoxides, e.g. isoC H1 sodium methoxide, sodium ethoxide, and the like, sodium O-2-chl0ro-4-nitrophenyl O-isopropyl methylphosphonothloate Carbonate, Potassium bicarbonate, Sodium hydroxide, P tassium amide, potassium hydroxide, etc., the tetra-substituted oniurn type salts of weak acids, e.g. tetramethylammonium hydroxide, tribenzylmethylammonium hydroxide, tetraethylammonium alkoxides, triphenylsulfonium hydroxide and the like.

Using the procedure set forth in the previous examples, 57 g. of 0,0 bis(2-chloro-4-nitrophenyl)methylphosphonothioate was refluxed for 77 hours with isopropanol previously reacted with 0.75 g. of sodium. There was obtained in a 77% yield a brown, oily product having I claim: a refractive Index of 15545 1. The method of preparing a mixed alkyl aryl alkyl- Example 4 phosphonate of the following formula:

H i /C CHzC1T2O\|SI R I', OAI cI-I /P0 c1 C1 wherein each of R and R represents an alkyl radical of from 1 to 18 carbon atoms, Ar represents an aromatic O-isoamyl O-2,4,5-tr1chl0rophenyl ethylphosphonothloate hydrocarbon residue selected from the class consisting The product of this example was prepared using 48.7 g. of a Phenyl radical and a p y radficfll and X is a of 0,0-bis(2,4,5-trichlorophenyl)ethylphosphonothioate chalwgfin selected from t class ponslstmg of Oxygen and 150 ml. of isoamylalcohol previously reacted with and Whlch comprlses l'eactlng PIldflr anhydrous 75 f Sodium. There was obtained 35 94% f conditions in the presence of an alkali metal salt of a a light yellow, oily Product having an zs f weak acid capable of forming a phenoxide ion with l 5 phenol as the catalyst and in approximately equal molar Exam? 3 amounts an aliphatic alcohol of the formula R-OH H wherein R has the significance as above set forth with C R an alkyl phosphonate of the formula:

/CHO\fi on, /P-ONO2 H /0Ar 0:115 R-P O-lsopropyl O-4-nltropheny1 ethylphosphonothloate The {ibove depicted was obtainefi by react wherein R, X, Ar have the values as above defined and mg a mixture of Of Q 'P 3 separating the resulting mixed alkyl aryl alkylphosphonate ethylphosphonothioate and 120 ml. of isopropanol prefrom the phenolic byproduct viously reacted with 1 g. of metallic sodium. After the 2' The method according to claim 1 wherein the cata mixture was refluxed for 47 hours, there was isolated a lyst is an alkali metal alkoxide. light Yellow the D of whlch 1S 3. The method according to claim 2 wherein the alkali Example 6 metal alkoxide is sodium alkoxide.

4. The method according to claim 1 wherein the reac- C C1 tion is carried out in the presence of excess alcohol as \i s r ii h d d 1 1 h h e met 0 accor ing to c aim w ereint e reac- CHaCH P O tion is carried out under reflux. z

O-2-chloro-4-nltrophenyl O-sec.-bntyl ethylphosphonotliloate (References on following page) References Cited by the Examiner UNITED OTHER REFERENCES STATES PATENTS Arbuzov et a1., Bull. Acad. Sci. (English Trans.),

Walsh 260-461.315 (1952) Hechenblelkner et 2 315 5 CHARLES B. PARKER, Primary Examiner. Hecker et a1. 26O-461L315 FRANK M. SIKORA, Assistant Examiner. 

1. THE METHOD OF PREPARING A MIXED ALKYL ARYL ALKYLPHOSPHONATE OF THE FOLLOWING FORMULA: 